Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects

We examined the association of apolipoprotein E (apo E) genotype with cognitive performance in Alzheimer9s disease (AD) and Mild Cognitive Impairment (MCI) patients and in normal subjects. One hundred fifty-seven AD patients, 35 MCI patients who developed AD during longitudinal follow-up, and 341 normal control subjects from the Mayo Clinic Alzheimer9s Disease Patient Registry were studied. All participants were typed for apo E using polymerase chain reaction-based assay. ϵ4+ and ϵ4— groups were compared on cognitive factor scores of Verbal Comprehension, Perceptual Organization, Attention/ Concentration, Learning, and Retention. Raw delayed verbal recall and visual confrontation naming scores supplemented these scores. Multivariate ANOVA was completed for cognitive scores. As expected, a main effect for diagnostic group was present across all scores. Multivariate main effects for age group and apo E genotype were also statistically significant. Subsequent within-group comparisons revealed no genotype differences for control subjects across all cognitive scores except raw delayed recall where an interaction indicated that older ϵ4+ control subjects actually scored better than younger ϵ4+ patients. Genotype differences were present for the Retention factor in the MCI sample and for Verbal Comprehension and Learning in the AD sample. In a combined cognitive impairment sample (AD + MCI), genotype differences were present for Verbal Comprehension, Learning, and Retention. Possession of an apo E ϵ4 allele did not appear to be associated with poorer cognitive performance among normal control subjects. In the AD and MCI samples, ϵ4+ status was associated with greater memory impairment in analyses including duration of illness as a covariate. In combined AD + MCI analyses, ϵ4 homozygosity was associated with poorer retention, learning, and verbal comprehension at a given disease duration. Possession of the ϵ4 genotype may influence cognition in a dose-response relationship.